In 1975, we reported that borderline hypertensives (BHT) respond to high salt intake with increases in forearm vascular resistance and arterial pressure whereas normotensive (NT) subjects decreased forearm resistance and did not increase arterial pressure. This study introduced two concepts regarding the mechanisms of salt-sensitivity vs. resistance in humans. 1) Contrasting vascular response was the hemodynamic hallmark of salt sensitivity vs. salt resistance. 2) There was an important role for neurogenic mechanisms with evidence for salt induced facilitation of neurogenic vasoconstriction in salt sensitive, but not in salt resistant subjects. The overall goal of this project is to elucidate the mechanisms and markers of the contrasting vascular and neural adjustments to high sodium intake in salt sensitive vs. salt resistant humans. We propose to study BHT vs. NT young adults and also to compare NT subjects with and without a history of hypertension in their parents. Subjects will be studied after achieving sodium balance on low salt and high salt diets. We plan: 1) To measure forearm vascular resistance at rest and in response to inhibition of baroreceptors by lower body negative pressure, 2) To measure renal blood flow, glomerular filtration rate, and urinary Na, K, and water excretion during inhibition of baroreceptors by upright posture and stimulation of low pressure baroreceptors by head-out water immersion, 3) To determine if high salt intake produces contrasting effects on muscle sympathetic nerve activity, measured directly by microneurography, in normotensives with and without parental hypertension, 4) to measure the circulating ouabain-like inhibitor at the end of each diet period to test whether salt-sensitive subjects have increased levels, 5) To measure circulating atrial natriuretic factor to see if it is subnormal in salt-sensitive individuals, 6) To measure Na-Na/Na-Li countertransport, ouabain sensitive Na transport, and intracellular Na in erythrocytes to determine if abnormalities in Na transport serve as markers in BHT and NT with hypertensive parents, 7) To measure beta adrenergic receptor sensitivity for agonists in lymphocytes to determine if reduced beta-receptor sensitivity characterizes salt sensitive subjects.